The goal of these studies is to provide insights into T-cell biology and examine the role of various cellular factors in modulation of HIV-1 replication in the context of T cell activation, using RNAi technology. We are developing a lentiviral vector-based system for the sustained delivery of siRNAs into target cells. This is a platform that may be used for knockdown of gene expression in target cells, including difficult to transfect cells including primary T cells. With this technology in place, it will be possible to study the role of various cellular factors in HIV-1 replication in a biologically relevant system. In particular we are looking at the role of transcription factors, NF-kB and NFATs. This technology may eventually be extended to examine various cellular pathways such as T cell activation pathways as well as to examine crucial questions in virus biology.